Understanding Probiotics and COVID-19 link: Key points for Indian Practitioners
While the recommendations regarding the strain, dose, and duration of probiotic are yet to be well established; given the large experience of clinical usage, and evidence for beneficial effects in various clinical settings, Lactobacillus and Bifidobacterium can safely be used 1
Severe acute respiratory syndrome Coronavirus-2 (SARS nCoV-2), causing Coronavirus disease 2019 (COVID-19) remains a continuously progressing pandemic with 25,118,689 (about 2.5 crores) cases and 844,312 (about 8.5 lakhs) deaths all over the world with a mortality rate of 3.4% as estimated by the WHO database at the end of August 2020 1 . The major reasons for massive impact of COVID-19 seem to be lack of preparedness for such unprecedented transmission, intrinsic virulence of the pathogen and its contagiousness, asymptomatic spreaders, unavailability of a vaccine, and lack of effective antiviral agents 2 . In the light of emerging pathophysiological targets in COVID-19, the consideration of probiotics seems justified and clinical evidence in this direction is evolving rapidly.
Gut-lung axis and gut microbiome in COVID-19
Along with alveolar epithelial cells, enterocytes in the gut also express angiotensin-converting enzyme 2 (ACE2) receptors, and SARS-CoV-2 RNA has been demonstrated in the faeces of infected patients 3 . Also, SARS-CoV-2 have the potential to invade enterocytes, and therefore, the gut may act as a reservoir of the virus 4 . Such interaction of SARS-CoV-2 with ACE2 receptors in the gut could be responsible for gastrointestinal symptoms, which are noted in up to 60% cases of COVID-19 and is often associated with increased severity of the infection 5 .
There is evidence available to indicate crosstalk between gut microbiota and lung, commonly referred to as the gut-lung axis. This axis is responsible for maintaining the host homeostasis and may be altered in disease. Such gut-lung interaction is bidirectional, and the gut plays a critical role in influencing lung disease. In diseased states, the gut microbiome patterns are altered, leading to dysbiosis, which causes translocation of endotoxins and microbial metabolites from the gut, which in turn affects the lung through haematological communication. Similarly, when inflammation occurs in the lungs (e.g., through respiratory viral infections), it causes disturbances in the gut microbiome 6
Therefore, such dysregulated & augmented inflammation, along with gut dysbiosis may be important pathophysiological processes in patients with COVID-19 leading to increased severity of illness and poor clinical outcomes 1
Probiotics in COVID-19
In the absence of proven effective therapy for COVID-19, the treatment is mainly supportive. Therefore, there is a need to continually explore alternative strategies which target pathophysiological pathways in patients with COVID-19 and they need to be tested. One such approach is the use of probiotics. 1
Probiotics exert their beneficial effects through multiple mechanisms including, manipulation and restoration of gut microbiota, by strengthening the intestinal barrier function, competing with pathogens for adhesion to gut epithelium and nutrition, suppressing opportunistic organisms, synthesizing and secretion of antimicrobial substances, supporting activation of mucosal immunity, and modulating innate and adaptive immune responses 7
Since the gut microbiome is altered in cases with COVID-19 3 , probiotics may help in restoring the gut microbiota, maintain a healthy gut-lung axis, leading to lesser translocation of primary and secondary pathogens across gut mucosa, and reduce the risk of developing secondary bacterial infections. 1
Modulation of inflammation by probiotics
As the occurrence of cytokine storm is fairly established in patients with severe COVID-19, the effect of probiotics on pro-inflammatory and immunoregulatory cytokines permits viral clearance and minimizes immune response-mediated tissue damage in the lungs and other target organs. Such immune-modulatory effects of probiotics might be relevant to prevent lung injury, acute respiratory distress syndrome (ARDS), and multiple organ failures which are complication endpoints of COVID-19 7
Antiviral effects of Probiotics:
Probiotics may act as antiviral agents by interfering with the entry of the virus into host cells and/or inhibiting viral replication. This may lead to a reduction in the spread of SARS-CoV-2 in the respiratory tract and gut. In addition, with the restoration of the gut and respiratory microbial harmony, immune function, and gut-lung axis, the course of COVID-19 may be altered 7
Most of the probiotic strains are generally safe even in the vulnerable patient groups and in-hospital care settings, including neonates, children, and adults. Many probiotic strains have indicated even beneficial effects in this settings 1 .
Rationale for use of Probiotics in COVID-19
Probiotics, by virtue of their action, are a potential strategy that needs to be tested in moderate to severe cases with COVID-19 by conducting well-designed clinical trials. Few registered trials are underway and evaluating the possible beneficial effects of probiotics supplementation in cases with COVID-19 1 .
A recent clinical trial which used a combination of multi-strain probiotics including Lactobacillus administered to hospitalised patients positive for COVID-19, resulted in an eightfold lower risk of developing respiratory failure compared to standard care, thus significantly improving clinical outcomes in COVID-19 infections 8
Probiotics – targeting the pathophysiological processes in the context of COVID-19 infections, are one of the strategies that exert beneficial effects by manipulation of the gut microbiota, activation of mucosal immunity, and modulation of the innate and adaptive immune response. Probiotics are the potential candidates which need to be tested more often in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, safety, and cost effectiveness 1 .
Final Remarks
Probiotics may have a beneficial role in the treatment of COVID-19 patients due to their antiviral activity, inflammation regulating effects and practical advantages like easy availability and inexpensiveness, making them a valid consideration for use in the Indian practice settings. While the recommendations regarding the strain, dose, and duration of probiotic are yet to be well established; given the large experience of clinical usage, and evidence for beneficial effects in various clinical settings, Lactobacillus and Bifidobacterium can safely be used (1)
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on probiotics, CLICK HERE
References:
Adapted from:
1 Angurana SK, Bansal A. Probiotics and COVID-19: Think about the link. Br J Nutr. 2020 Sep 14:1-26. doi: 10.1017/S000711452000361X. Epub ahead of print. PMID: 32921328.
2 Infusino F, Marazzato M, Mancone M, Fedele F, Mastroianni CM, Severino P, et al. Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review. Nutrients. 2020;12(6).
3 Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020;285:198018
4 Lin L, Jiang X, Zhang Z, Huang S, Zhang Z, Fang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997-1001
5 Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-32
6 Keely S, Talley NJ, Hansbro PM. Pulmonary-intestinal crosstalk in mucosal inflammatory disease. Mucosal Immunol. 2012;5(1):7-18
7 Baud D, Dimopoulou Agri V, Gibson GR, Reid G, Giannoni E. Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. Front Public Health. 2020;8:186.
8 d'Ettorre G, Ceccarelli G et al, (2020) Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19. Front. Med. 7:389. doi: 10.3389/fmed.2020.003
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